Recent study suggests that synaptic transmission between muscle-spindle afferents and spinal motoneurons is enhanced after a prolonged period of suppression. This inverse relationship between synaptic strength and activity is unlike others that have been documented, and it may provide new explanations for the reaction of the central nervous system to injury or disease. Specifically, certain central neurons temporarily silenced by deprivation of their excitatory input may develop a much stronger influence in a circuit when their activity is restored. The long-term objective of this study is to establish the rules and understand the mechanisms by which activity regulates transmission in neural circuits. Monosynaptic transmission onto spinal motoneurons from selected group Ia muscle-spindle afferents will be completely suppressed for two weeks in adult cats. The suppression will be achieved by blocking action potential conduction in one muscle nerve using the neurotoxin tetrodotoxin (TTX). At the end of the treatment period cats will be anesthetized, and the excitatory postsynaptic potentials (EPSPs) produced in motoneurons by treated and untreated afferents will be measured in vivo by intracellular recording. Three experiments are designed to examine the mechanism(s) accounting for enhanced transmission from previously inactive Ia afferents. First, it will be determined whether the enlargement of composite Ia EPSPs (produced by stimulating all group I afferents that supply one muscle) is caused by an increase in the synaptic strength of individual afferents, or by the activation of more afferent connections, or both. Second, the modulation of EPSP size during acute high-frequency stimulation of single afferents will be examined to further characterize the transmission behavior of chronically inactive synapses. Both of those experiments will use the spike-triggered averaging technique to resolve the EPSPs produced in a motoneuron by a single Ia afferent. Third, the synaptic action of untreated afferents will be used to identify localized postsynaptic changes in motoneurons that receive synapses from inactivated afferents. A fourth experiment will determine whether synaptic enhancement persists after synaptic activity is restored.